..These mice also can serve as a valuable model to dissect the mechanism of OGF-OGFr action and may be important in understanding the etiology, pathogenesis, and treatment of epithelium-related diseases...

Modulation of the opioid growth factor ([Met(5)]-enkephalin)-opioid growth factor receptor axis: novel therapies for squamous cell carcinoma of the head and neck

Patricia J McLaughlinDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USAHead Neck 34:513-9. 2012

..This study investigated modulation of the OGF-OGFr system by (1) exogenous OGF, (2) upregulation of OGFr using imiquimod, or (3) intermittent opioid receptor blockade with a low dose of naltrexone on progression of established SCCHN...

..These results suggest that the target of imiquimod on DNA synthesis is dependent on an opioid receptor-mediated pathway, and infers that imiquimod is reliant on the OGF-OGFr axis for modulating cell proliferation...

Opioid growth factor (OGF) inhibits the progression of human squamous cell carcinoma of the head and neck transplanted into nude mice

..These data suggest that topical application of NTX is a non-toxic and efficacious facilitator for healing full thickness wounds in T1D, with wound contraction serving as a particular target of NTX action...

..This study compared protein and gene expression of OGFr in surgical specimens of human squamous cell carcinoma of the head and neck (SCCHN) with normal epithelium...

Naltrexone and insulin are independently effective but not additive in accelerating corneal epithelial healing in type I diabetic rats

Matthew S KlocekDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USAExp Eye Res 89:686-92. 2009

..These data demonstrate that although NTX or INS accelerates wound healing, concomitant application of NTX and INS to corneal abrasions in diabetic animals does not have an additive effect on re-epithelialization...

..Complications of diabetes include an increased risk of delayed corneal epithelial wound healing. This study examined the efficacy of naltrexone (NTX), an opioid antagonist, by topical application in facilitating the repair of such lesions...

..This exciting new knowledge of the mechanism of imidazoquinolines has important physiological relevance, and allows strategies to be developed for the use of these agents that will enhance effectiveness as well as attenuate side-effects...

Opioid growth factor enhances tumor growth inhibition and increases the survival of paclitaxel-treated mice with squamous cell carcinoma of the head and neck

..These data are the first to report that the OGF-OGFr system is a native biological regulator of cell proliferation in human ovarian cancer. This information will be important in designing treatment strategies for this deadly disease...

Topical application of naltrexone facilitates reepithelialization of the cornea in diabetic rabbits

I S ZagonDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USABrain Res Bull 81:248-55. 2010

..These studies set the stage for clinical trials using NTX as a therapy for diabetic keratopathy...

Prevention of exuberant granulation tissue and neovascularization in the rat cornea by naltrexone

..The identification of this native biological system in neoplasia may be important in understanding the pathophysiology of neoplasia, and in designing treatment modalities that utilize the body's own chemistry...

Prevention and delay in progression of human pancreatic cancer by stable overexpression of the opioid growth factor receptor

Ian S ZagonDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USAInt J Oncol 33:317-23. 2008

..These data support OGFr gene function as a regulator of cell proliferation that impacts on tumorigenic expression, and suggest that molecular and pharmacological manipulation of OGFr may prevent or delay human pancreatic cancer...

..These data identify OGFr at the molecular level as integral to regulating the cell replication of human pancreatic cancer, and support treatment modalities that amplify OGFr in order to decrease the growth of these neoplasias...

Regulation of cell proliferation by the opioid growth factor receptor is dependent on karyopherin beta and Ran for nucleocytoplasmic trafficking

..RhoOGF clathrin-mediated endocytosis was unrelated to endosomal or Golgi pathways. Taken together, these results suggest that OGF enters cells by active transport in a saturable manner that requires clathrin-mediated endocytosis...

Diabetic keratopathy and treatment by modulation of the opioid growth factor (OGF)-OGF receptor (OGFr) axis with naltrexone: a review

Patricia J McLaughlinDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, USABrain Res Bull 81:236-47. 2010

..g., vitrectomy), and that conventional therapies such as artificial tears and bandage contact lenses often fail, topical application of NTX merits clinical consideration...

Ian S ZagonDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, 17033, USACornea 24:614-9. 2005

..This study was designed to determine at the molecular level whether interactions between the opioid growth factor (OGF) and OGF receptor (OGFr) play a role in regulating DNA synthesis in the homeostasis of the corneal epithelium...

..These data are the first to report that the OGF-OGFr system is a native biological regulator of cell proliferation in HCC. The findings may provide important insight in designing treatment strategies for this deadly disease...

Fan ChengDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USACancer Res 67:10511-8. 2007

..These data are the first to reveal that the target of cell proliferative inhibitory action of OGF in human HNSCC is a cyclin-dependent kinase inhibitory pathway, and this may be useful in the diagnosis and treatment of HNSCC...

..In summary, preclinical data support the transition of these novel therapies for treatment of human ovarian cancer from the bench to bedside to provide additional targets for treatment of this devastating disease...

Astrocyte proliferation is regulated by the OGF-OGFr axis in vitro and in experimental autoimmune encephalomyelitis

Naltrexone, an opioid antagonist, facilitates reepithelialization of the cornea in diabetic rat

Ian S ZagonDepartment of Neuroscience and Anatomy, The Pennsylvania State University College of Medicine, Hershey 17033, USADiabetes 51:3055-62. 2002

..These results indicate a delay in reepithelialization that is dependent on the duration of diabetes and that intervention of endogenous opioid-receptor interfacing with an opioid antagonist can facilitate the process of wound healing...

Dependence on nuclear localization signals of the opioid growth factor receptor in the regulation of cell proliferation

..These results indicate that the regulation of cell proliferation by the OGF-OGFr axis is dependent on nucleocytoplasmic translocation and reliant on the integrity of two NLSs in OGFr to interact with transport receptors...

David GoldenbergDivision of Otolaryngology, Department of Surgery, H091, College of Medicine, The Penn State University, Hershey, Pennsylvania 17033, USAThyroid 18:1165-70. 2008

..In the present study we examined the presence and distribution of OGF and OGFr in nonmedullary thyroid cancer, including papillary, follicular, and anaplastic, as well as thyroid tissue from patients with nonmalignant disease...

..Given the parallels between short-term NTX in vitro and LDN in vivo, we now demonstrate at the molecular level that the OGF-OGFr axis is a common pathway that is essential for the regulation of cell proliferation by NTX...

Ian S ZagonDepartment of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA 17033, United StatesBrain Res Bull 72:18-24. 2007

..Thus, recurrent erosion following abrasion of the diabetic cornea, with preservation of the basal lamina, cannot be explained by structural abnormalities in the reformation of the epithelial adhesion complex...

Ian S ZagonDepartment of Neural and Behavioral Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USAImmunobiology 216:173-83. 2011

..Thus, at least exogenous OGF and perhaps endogenous OGF by paracrine/endocrine sources, can be an immunosuppressant. Modulation of the OGF-OGFr axis may be a novel paradigm for the treatment of autoimmune diseases...

..This report reviews the history of OGF-OGFr, examines emerging insights into the mechanisms of action of opioid peptide-receptor interfacing, and discusses the clinical significance of these observations...